Paediatrica Indonesiana
VOLUME 54
Efficacy of mebendazole and levamisole, alone or in
combination, for soil-transmitted helminthiasis
Ifo Faujiah Sihite, Muhammad Ali, Ayodhia P. Pasaribu, Syahril Pasaribu, Chairuddin P. Lubis
Abstract
Background The World Health Organization (WHO)
recommends four, single-dose drugs (albendazole, levamisole,
mebendazole, and pyrantel pamoate) for management of soil-
transmitted helminthiasis (STH). Previous studies have shown
varied and inconsistent outcomes of these STH treatments.
Objective To compare the efficacy of mebendazole and levami-
sole, alone or in combination, for the treatment of STH.
Methods An open randomized controlled trial was conducted
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School-aged children with STH infection were randomized into
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January ‡ NUMBER 1
Original Article
S
oil-transmitted helminths (STH) are a group
of parasitic nematode worms causing human
infection through contact with parasite eggs
or larvae that thrive in the warm and moist
soil of the world’s tropical and subtropical countries.
Of particular worldwide importance are Ascaris
lumbricoides, Trichuris trichiura, Necator americanus,
and Ancylostoma duodenale.1
In 1999, the WHO estimated that these in-
IHFWLRQVUHSUHVHQWHGPRUHWKDQRIWKHGLVHDVH
PJJURXS,,UHFHLYHGDVLQJOHGRVHRIOHYDPLVROHPJNJ
and group III received a single dose of mebendazole-levamisole
combined. Stool samples were collected at baseline, and the
1stndrd, and 4th weeks after treatment and examined by the
Kato-Katz technique. Statistical analyses were Kruskal-Wallis
test for cure rate and Analysis of Variance (ANOVA) test for
egg reduction rate.
Results 67+ZDVGLDJQRVHGLQFKLOGUHQZLWKWKHIROORZLQJ
burden from all tropical diseases, excluding ma-
laria. An estimated 4.5 billion individuals might
be infected with A. lumbricoidesFORVHWRPLOOLRQ
with T. trichiura DQG PRUH WKDQ  PLOOLRQ ZLWK
hookworm.5 School-aged children in developing
countries bear the greatest health burden due to
helminth infections. Factors influencing the preva-
parasite species: AscariasisFKLOGUHQ Trichuriasis (58 lence of STH are hygiene, sanitation, socioeconomic
FKLOGUHQDQGPL[HGLQIHFWLRQFKLOGUHQ:H level, educational level, and ecosystem differences.
found no hookworm infection in any of our subjects. Groups I
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In Indonesia, the prevalence of STH remains high at
HJJUHGXFWLRQUDWHDQGFXUHUDWHDQG
respectively) at 4th week of treatment.
Conclusion A single dose of mebendazole alone and combined
with levamisole have better efficacy compared to a single dose of This study was presented at 15th Indonesian Congress of Pediatrics
levamisole for the treatment of STH. The highest efficacy of these (KONIKA XV) Manado, July 11th – 14th
treatments is noted at the 4th week after drug administration.
[Paediatr Indones. 2014;54:9-14.]. From Department of Child Health, University of North Sumatera Medical
6FKRRO+$GDP0DOLN+RVSLWDO0HGDQ,QGRQHVLD

Reprint requests to: Ifo Faujiah Sihite. Department of Child Health,

Keywords: soil-transmitted helminth, mebendazole, 8QLYHUVLW\RI1RUWK6XPDWHUD0HGLFDO6FKRRO+$GDP0DOLN+RVSLWDOJl.
levamisole, combination %XQJD/DX1R0HGDQ7HO
)D[E-mail: ragazzoivoy@yahoo.com.

Paediatr Indones, Vol. 54, No. 1, January 2014‡9

 Ifo Faujiah Sihite et al: Efficacy of mebendazole and levamisole for soil-transmitted helmenthiasis

DQGLVUHODWHGWRWKHORFDWLRQDQGFOHDQOLQHVV  PJ JURXS ,, UHFHLYHG VLQJOHGRVH OHYDPLVROH

of the environment.
Four, single-dose antihelminthic drugs, albenda-
zole, levamisole, mebendazole, and pyrantel pamoate,
are available for the treatment of STH infections in
pharmacological-based control programs.8,9 These
drugs are recommended by the WHO.9
The objective of this study was to compare the
efficacy of mebendazole and levamisole, alone or in
combination, for the treatment of STH.
Methods
We conducted an open randomized controlled trial
in Secanggang, North Sumatera from August until
2FWREHU  6XEMHFWV ZHUH SULPDU\ VFKRRODJHG
children infected with STH. The inclusion criteria for
subjects were primary school aged children, infected
with STH, and had not taken antihelminthics for at
least the one month prior to the study. Patients were
excluded if they refused to swallow the antihelminthic
or submit stool specimens after treatment, or had
diarrhea, cough, or fever.
Prior to treatment, each participant underwent
 PJNJ DQG JURXS ,,, UHFHLYHG VLQJOHGRVH
mebendazole-levamisole combined.
Subjects’ stool specimens were collected and
examined at baseline, and on the 1stndrd, and 4th
weeks after treatment. Outcome measures were cure
rate and egg reduction rate. Subjects were considered
to be cured when no worm eggs were found in their
stool specimens. All adverse reactions were recorded.
Written consent was obtained from subjects’ parents.
This study was approved by the Medical Ethics
Committee of the University of North Sumatra
Medical School.
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Statistical analyses were carried out by Kruskal-Wallis
and Analysis of Variance (ANOVA) tests. Differences
were considered to be statistically significant at P
YDOXHVDQG&,
Results
We performed stool examinations on 415 primary
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infections. We enrolled and randomly assigned them
anthropometric assessment and completed a LQWR WKUHH JURXSV *URXS ,  FKLOGUHQ UHFHLYHG
questionnaire on socioeconomic and hygiene status. VLQJOHGRVH PHEHQGD]ROH  PJ JURXS ,, 
Participants were randomly assigned following a simple FKLOGUHQ  UHFHLYHG VLQJOHGRVH OHYDPLVROH  PJ
randomization procedure (random table) into three NJDQGJURXS,,,FKLOGUHQUHFHLYHGVLQJOHGRVH
groups. Group I received single-dose mebendazole mebendazole-levamisole (Figure 1).

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10‡Paediatr Indones, Vol. 54, No. 1, January 2014

 Ifo Faujiah Sihite et al: Efficacy of mebendazole and levamisole for soil-transmitted helmenthiasis

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infection. The baseline characteristics of each group
were similar. Number of males and females in all groups
was almost the same. The average age of subjects was
\HDUVZLWKWKHSHUFHQWDJHRIERG\ZHLJKWEDVHGRQ
height for all groups within normal limits. There were
no statistically significant differences in the average
number of eggs between the groups before treatment
(Table 1).
Drug effectiveness based on egg reduction rate
(Table 2) was significantly different between group
III (combination treatment) from group II (levamisole
alone) each of the 1st to 4th week after treatment.
There was no significant difference in egg reduction

Table 1$CUGNKPGEJCTCEVGTKUVKEUQHUWDLGEVU
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A. lumbricoides 
 
 

T. trichiura 
 
 

A. lumbricoides + T. trichiura 
 
 


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Paediatr Indones, Vol. 54, No. 1, January 2014‡11

 Ifo Faujiah Sihite et al: Efficacy of mebendazole and levamisole for soil-transmitted helmenthiasis
rate between group III and group I (mebendazole
alone) each of the 1st to 4th weeks after treatment.
We found significant differences in cure rates
between group III (combination treatment) and group
II (levamisole alone) each of the 1st to 4th weeks after
treatment. No significant differences were found
between group I (mebendazole alone) and group III
(Table 3).
Discussion
We found the prevalence of STH in our study to
EH  FRPSULVHG RI  DVFDULDVLV 
WULFKXULDVLV DQG  PL[HG LQIHFWLRQ Human
intestinal helminths and malaria are among the
most common infections in the developing world.
One-third of the world’s population is infected
with one or more species of intestinal helminths,11
and children are reported to have a prevalence rate
UDQJLQJEHWZHHQInfection with T. trichiura
and A. lumbricoides typically reaches the highest
LQFLGHQFHDWWR\HDUVRIDJH
We hoped that our study results would help
guide the WHO program, so schoolaged children
were selected as the study sample since they are at
PHQGHGLQFKLOGUHQPRQWKVRIDJH The goal
of treatment for STH infections is to remove adult
worms from the gastrointestinal tract. The drugs most
commonly used for the eradication of STH infections
are mebendazole and albendazole. Both agents are
effective against ascaris in a single dose. However, in
hookworm infections, a single dose of mebendazole
has a low cure rate, and albendazole is more effec-
tive. Conversely, a single dose of albendazole is not
effective in many cases of trichuriasis. Both pyrantel
pamoate and levamisole are regarded as alternative
drugs for the treatment of hookworm and ascaris in-
fections, although the former is not effective for the
treatment of trichuriasis and their doses are based on
body weight.1
Two indicators used to determine the efficacy of
an antihelminthic in human medicine are the cure
rate (CR) and the egg reduction rate (ERR).18 A
study in Zanzibar showed very high efficacy of me-
bendazole and levamisole alone or in combination
against A. lumbricoides(55
&5     IRU OHYDPLVROH PHEHQ-
dazole, and mebendazole-levamisole combination,
respectively). Mebendazole alone and in combination
with levamisole had better efficacy than levamisole
alone for T. trichiura LQIHFWLRQ (55  DQG 
high risk of STH infection. The mean age of subjects
ZDV\HDUVZLWKVLPLODULQFLGHQFHEHWZHHQPDOHV
and females. The World Health Assembly urged the
international community to take firm action against
67+LQIHFWLRQVLQ6LQFHWKHQWKH3DUWQHUVIRU
Parasite Control (PPC) set out to regularly deworm
PLOOLRQVFKRRODJHGFKLOGUHQDWULVNRI67+DQG
VFKLVWRVRPLDVLV E\  The WHO recommends
mass treatment of children in school, where the pre-
valence of infection with schistosomes or intestinal
QHPDWRGHVLVRUJUHDWHU14
Antihelminthics used in this study were
single-dose mebendazole and levamisole, alone or in
combination. Both the selection of drugs and doses
were based on WHO recommendations. Effective,
YVUHVSHFWLYHO\8VLQJDFRPELQDWLRQWUHDW-
ment, the egg reduction rate for hookworm infection
ZDVZLWK&5ZLWKVLJQLILFDQWO\ORZHU
(55DQG&5IRUHLWKHUGUXJDORQH(55&5
IRUOHYDPLVROHDQG(55&5IRU
mebendazole).8
0RUH WKDQ  FOLQLFDO WULDOV VKRZHG D KLJK
efficacy of levamisole against A. lumbricoides and
KRRNZRUPLQIHFWLRQV&XUHUDWHRIDQG(55
RIZLWKDVLQJOHGRVHKDYHEHHQUHSRUWHGIRU
A. lumbricoides infection. For hookworm infection,
&5LQWKHUDQJHRIDQG(55KDYH
been reported. Levamisole had a varied effect against
T. trichiuraZLWK&5RIDQG(55RI19 In
an Iranian study, treatment of STH with a single-dose
broad-spectrum, single-dose, safe, and relatively in- RI OHYDPLVROH  PJNJ VKRZHG RI KLJK HIILFDF\
expensive drugs are now available for the treatment of ZLWK&5RIIRUKRRNZRUPLQIHFWLRQVIRU
helminth infections.15 The four drugs recommended DVFDULDVLVDQGIRUWULFKXULDVLV
E\ :+2 IRU WUHDWPHQW DUH DOEHQGD]ROH  PJ In our study at the end of the 4th week of stool
OHYDPLVROHPJNJPHEHQGD]ROHPJDQG H[DPLQDWLRQ WKH HJJ UHGXFWLRQ UDWHV ZHUH 
S\UDQWHOSDPRDWHPJNJ All four anthelmin- DQGIRUPHEHQGD]ROHDORQHOHYDPLVROH
thics are given as a single dose and are not recom- alone, and the combination, respectively. Cure rates

12‡Paediatr Indones, Vol. 54, No. 1, January 2014

 Ifo Faujiah Sihite et al: Efficacy of mebendazole and levamisole for soil-transmitted helmenthiasis
ZHUH   DQG  IRU PHEHQGD]ROH
alone, levamisole alone, and the combination,
respectively. Mebendazole alone and in combination
with levamisole were more effective than levamisole
alone for ascariasis and trichuriasis STH infections.
The efficacy of mebendazole did not differ significantly
from that of its combination with levamisole.
Overall, side effects of antihelminthic drugs were
negligible and important adverse events were virtually
nonexistent. However, the safety of anthelminthic
drugs is of utmost importance because large portions
of the population are normally treated.15 No adverse
events were noted in our study.
A limitation of this study was that no blinding
was done, so we cannot exclude the possibility of
bias. Also, we did not assess the effectiveness of
anthelminthics based on worm type. We only assessed
the effect of worm infection on the occurrence of
malnutrition. The malnutrition status was assessed
by the percentage of body weight according to height.
We found good nutritional status for all three groups
of subjects studied. Further research will be needed
to assess the effectiveness of anthelminthics by worm
type and the effect of worm infections on children.
In conclusion, a single dose of mebendazole
transmitted helminth infections: systematic review and
PHWDDQDO\VLV-$0$
 00DUGLDQD''MDULVPDZDWL3UHYDOHQVLFDFLQJXVXVSDGD
murid sekolah dasar wajib belajar pelayanan gerakan terpadu
pengentasan kemiskinan daerah kumuh di wilayah DKI
-DNDUWD-XUQDO(NRORJL.HVHKDWDQ
 )LUPDQV\DK , *LQWLQJ 6$ /XELV 0 /XELV ,= 3DVDULEX 6
Lubis CP. Factor associated with the transmission of soil-
transmitted helminthiasis among schoolchildren. Paediatr
,QGRQHV
8. Albonico M, Bickle Q, Ramsan M, Montresor A, Savioli L,
Taylor M. Efficacy of mebendazole and levamisole alone or
in combination against intestinal nematode infections after
repeated targeted mebendazole treatment in Zanzibar. Bull
:RUOG+HDOWK2UJ
9. Albonico M, Bickle Q, Haji HJ, Ramsan M, Khatib KJ,
Montresor A, et al. Evaluation of the efficacy of pyrantel-
oxantel for the treatment of soil-transmitted nematode
LQIHFWLRQV7UDQV56RF7URS0HG+\J
 6\DULI$(O\VDEHWK$QWHOPLQWLN,Q*XQDZDQ6*6HWLDEXG\
R, Nafrialdi, Elysabeth, editors. Farmakologi dan terapi. 5th
HG-DNDUWD*D\D%DUXS
11. Zaman V. Nematoda. ,Q$QZDU&0XUVDO<HGLWRUV$WODV
SDUDVLWRORJLNHGRNWHUDQ-DNDUWD+LSRNUDWHVS

and its combination with levamisole have a better
efficacy than a single dose of levamisole alone for STH
treatment. The highest efficacy of these treatments is
noted at the 4th week after drug administration.
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1. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A,
Diemert D, et al. Soil-transmitted helminth infections:
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S
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%0-
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 0RQWUHVRU$&URPSWRQ':7+DOO$%XQG\'$36DYLROL
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Savioli L. Controlling soil-transmitted helminthiasis in pre-
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PA. Oral drug therapy for multiple neglected tropical diseases:
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14‡Paediatr Indones, Vol. 54, No. 1, January 2014